Despite improvements in morbidity and mortality from conditions other than cardiovascular diseases, both the incidence and prevalence of ESRD are progressively rising, as is its economical burden. In addition, cardiovascular morbidity and mortality among ESRD patients remain high. Management of conventional risk factors such as hypertension, diabetes, and dyslipidemia has not been shown to be sufficient to prevent the excess CVD mortality in ESRD patients. Therefore, there is a compelling need to study and target additional cardiovascular risk factors that can account for the increased mortality in ESRD patients. Vitamin B deficiency and resistant hyperhomocysteinemia may contribute to the increase in cardiovascular disease mortality, as well as the reduction of patients' perception of HRQOL. Treatment with B-complex vitamins is safe and inexpensive, and, more importantly, may ultimately reduce the progression of atherosclerosis and cardiovascular events. It is important to conduct a prospective, randomized placebo-controlled clinical trial to study the effects of B-Vitamins on atherosclerosis, cardiovascular disease outcome and health-related quality of life. The proposed study may also provide additional insights into the mechanisms responsible for cardiovascular diseases in ESRD patients.